A Double-Blind, Randomized, Active- and Placebo-Controlled, Multiple-Dose Multi-Center Phase 3 Study of the Safety and Efficacy of CL-108 in the Treatment of Moderate to Severe Acute Pain and Opioid-Induced Nausea and Vomiting (OINV)

INCLUSION CRITERIA

- Informed Consent: Signed consent obtained at screening prior to any procedures being
performed.

- Gender: Male or non-pregnant and non-lactating female. A female of child-bearing
potential is eligible to participate in this study if she has a negative urine
pregnancy test and is using an acceptable method of birth control (i.e., oral,
transdermal, or implanted contraceptives, intrauterine device, diaphragm, condom,
abstinence, or surgical sterilization)

- Age: 18 years or older

- OINV Status: At risk of OINV on the Nausea Prone Questionnaire (NPQ)

- Foot Condition: Surgical extraction of a unilateral first metatarsal bunion confirmed
by foot x-ray (assessed by surgeon prior to surgery)

- Pain Severity: Presence of moderate or severe pain (i.e., ≥ 4 on the baseline
numerical pain intensity rating scale [PI-NRS])

- Pain Confirm: Rating ≥ 50 mm on the baseline visual analog pain intensity scale
(PI-VAS)

- Diary Completion: Be willing and able to record safety and efficacy information in
the In-patient and Outpatient Diaries

- Safe Transportation: Patient must have arrangements for transportation home from the
research center accompanied by a responsible adult

EXLUSION CRITERIA

- Medical Condition: Presence of a serious medical condition (e.g., poorly controlled
hypertension or diabetes, neurological disease including Parkinson's or other
condition associated with a movement disorder, significantly impaired cardiac, renal,
hepatic, respiratory, or thyroid function)

- Infection: Acute local infection at the time of surgery that could confound
post-surgical evaluation.

- Drug Allergy: History of hypersensitivity or allergy to an opioid drug such as
hydrocodone, promethazine, acetaminophen, ondansetron, NSAID (such as ibuprofen,
including aspirin) or ketorolac or history of a dystonic/dyskinetic reaction to prior
anti-emetic or anti-psychotic medication

- Contraindicated Drugs: Use (within 24 hours of the surgical procedure) of any
confounding prescription or non-prescription drug (e.g., analgesic, anti-emetic,
sedating antihistamine, sedative, alcohol, CNS/psychotropic agent, including sleep
aides, benzodiazepines, performance/attention enhancers, marijuana, anti-depressants)
or any drug contraindicated with hydrocodone, acetaminophen, or promethazine (except
for pre-op medications). Antibiotic prophylaxis for endocarditis (except if known to
cause nausea) and ASA 62.5 mg for cardiovascular prophylaxis are permitted during the
study.

- History of drug or alcohol abuse

- Caffeine Use: Ingestion of any caffeine-containing beverage or chocolate since
mid-night before the operation

- Investigation Drug Use: Use of an investigational drug within the past 30 days

- Participated in Study:Previous participation in this study

- Pregnancy, Lactation: Women who are pregnant or lactating

- Participant Relation: Employee at the research center or of Charleston Laboratories
or relative of the Principal Investigator, Sub-Investigators, or research staff who
is directly involved in this study